The role of brain-derived neurotrophic factor in learned fear processing: an awake rat fMRI study

Autor:	Cyril Pernet, Heather C. Whalley, Nichola M. Brydges, Mark Day, Scott J. Baker, Ross J. Lennen, Ian Marshall, Jeremy Hall, Ana M. Basso, Anjanette P. Harris, Maurits A. Jansen, Megan C. Holmes
Rok vydání:	2016
Předmět:	0301 basic medicine Brain-derived neurotrophic factor Classical conditioning Amygdala Periaqueductal gray Peripheral 03 medical and health sciences Behavioral Neuroscience 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure nervous system Neurology Neurotrophic factors Genetics medicine Biomarker (medicine) Wakefulness Psychology Neuroscience 030217 neurology & neurosurgery
Zdroj:	Genes, Brain and Behavior. 15:221-230
ISSN:	1601-1848
Popis:	Brain-derived neurotrophic factor (BDNF) signaling is implicated in the aetiology of many psychiatric disorders associated with altered emotional processing. Altered peripheral (plasma) BDNF levels have been proposed as a biomarker for neuropsychiatric disease risk in humans. However the relationship between peripheral and central BDNF levels and emotional brain activation is unknown. We used heterozygous BDNF knockdown rats (BDNF+/- ) to examine the effects of genetic variation in the BDNF gene on peripheral and central BDNF levels and emotional brain activation as assessed by awake fMRI. BDNF+/- and control rats were trained to associate a flashing light (conditioned stimulus; CS) with foot-shock, and brain activation in response to the CS was measured 24h later in awake rats using fMRI. Central and peripheral BDNF levels were decreased in BDNF+/- rats compared to control rats. Activation of fear circuitry (amygdala, periaqueductal gray, granular insular) was seen in control animals, however activation of this circuitry was absent in BDNF+/- animals. Behavioral experiments confirmed impaired conditioned fear responses in BDNF+/- rats, despite intact innate fear responses. These data confirm a positive correlation (r = 0.86, 95% CI [0.55, 0.96]; P = 0.0004) between peripheral and central BDNF levels and indicate a functional relationship between BDNF levels and emotional brain activation as assessed by fMRI. The results demonstrate the use of rodent fMRI as a sensitive tool for measuring brain function in preclinical translational studies using genetically modified rats and support the use of peripheral BDNF as a biomarker of central affective processing.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5bf1d7a68366432a95b0744e7128a4e7 https://doi.org/10.1111/gbb.12277 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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